Molecular characterization of dedifferentiated mucoepidermoid carcinoma of the trachea using laser microdissection-based TP53 mutation analysis

Cancer Science Institute of Singapore (CSI), National University of Singapore (NUS), Singapore.
Histopathology (Impact Factor: 3.45). 10/2009; 55(4):472-5. DOI: 10.1111/j.1365-2559.2009.03385.x
Source: PubMed
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    • "In the first case, an image cytometric analysis revealed that the LG and HG carcinomas were diploid and aneuploid, respectively [48]. In addition, the second case involved TP53 gene mutations and corresponding protein overexpression [49]. Since the CRTC1 (also known as MECT-1)-MAML2 fusion gene is considered to be a highly specific diagnostic marker for MEC [65–68], the identification of the fusion gene may be useful for the diagnosis of the “dedifferentiated” MEC. "
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    ABSTRACT: "Dedifferentiation" and/or high-grade transformation (HGT) has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous low-grade adenocarcinoma, myoepithelial carcinoma, low-grade mucoepidermoid carcinoma and hyalinizing clear cell carcinoma, although the phenomenon is a rare event. Recent authors tend to preferably use the term HGT instead of "dedifferentiation" in these cases. HGT-tumors are composed of conventional carcinomas juxtaposed with areas of HG morphology, usually either poorly differentiated adenocarcinoma or "undifferentiated" carcinoma, in which the original line of differentiation is no longer evident. The HG component is generally composed of solid nests, sometimes occurring in cribriform pattern of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli and abundant cytoplasm. Frequent mitoses and extensive necrosis is evident. The Ki-67 labeling index is consistently higher in the HG component. p53 abnormalities have been demonstrated in the transformed component in a few examples, but the frequency varies by the histologic type. HER-2/neu overexpression and/or gene amplification is considerably exceptional. The molecular-genetic mechanisms responsible for the pathway of HGT in salivary gland carcinomas largely still remain to be elucidated. Salivary gland carcinomas with HGT have been shown to be more aggressive than conventional carcinomas with a poorer prognosis, accompanied by higher local recurrence rate and propensity for cervical lymph node metastasis, suggesting the need for wider resection and neck dissection.
    Head and Neck Pathology 07/2013; 7(Suppl 1). DOI:10.1007/s12105-013-0458-8
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    • "Positive expression was observed in dedifferentiated/transformed and conventional area of AdCC, AcCC, and EMC [5] [8] [9] [21] [25] [28]. However, in the MEC, Subramaniam et al. did not find positive expression in the dedifferentiated area [54]. The precise mechanisms responsible for the observed cyclin D1 overexpression in dedifferentiated/high-grade transformed salivary gland tumors (Table 1) are not fully established; a role in dedifferentiation of AdCC has been suggested in early studies [2] [21]. "
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    ABSTRACT: The concept of dedifferentiation had previously been used in salivary gland carcinomas. Recently, the term "high-grade transformation" was introduced for adenoid cystic carcinoma, acinic cell carcinoma, epithelial-myoepithelial carcinoma, and polymorphous low-grade adenocarcinoma and may better reflect this phenomenon, although transformation into moderately differentiated adenocarcinoma (i.e., not "high grade") has also been described. Among the immunohistochemical markers, Ki-67 seems to be the only one that can help distinguish between the conventional and transformed components; however, the combination of morphological criteria is still sovereign. The overexpression of p53 was observed in the transformed component in all tumor types studied, despite few cases having been demonstrated to carry mutations or deletions in TP53 gene. Genetic studies in salivary gland tumors with dedifferentiation/high-grade transformation are rare and deserve further investigation. This paper aims at providing an overview on the recent concepts in histopathological classification of salivary gland tumors, complemented by immunohistochemical and genetic findings.
    Pathology Research International 08/2011; 2011(2):325965. DOI:10.4061/2011/325965
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    ABSTRACT: We present a 45 year old female patient with a nasal carcinoma showing high-grade/anaplastic histomorphological features and with a distinct myoepithelial immunohistochemical phenotype including positivity for smooth muscle actin, p63, S100 protein with no sustentacular pattern, calponin, cytokeratin 14, vimentin and cytokeratins (AE1-3 and CK5/6). A minority (<5%) of the cells showed focal and variable immunoreactivity for EMA with no cuticular/canalicular pattern. Bcl-2, CD99, CD117 and CD56 were variously positive, but chromogranin and synaptophysin were negative. Weak to moderate nuclear p53 immunoreactivity was seen in 50% of tumor cells. Mib-1/Ki-67 showed an average proliferation of 60-70%. Fluorescent in situ hybridization revealed no EWS-gene translocation. In situ hybridization for EBER was negative.
    Head and Neck Pathology 11/2010; 5(2):144-53. DOI:10.1007/s12105-010-0226-y
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